When the rate of metabolism of a substance is diffusion limited, the pattern of metabolism may change with increasing concentrations of the substance even when its total metabolic clearnance is not changed. The objective of this project is to determine whether the metablism of furosemide by mouse hepato-cytes is diffusion limited. the covalent binding of (C-14)-labeled furosemide to isolated hapatocytes will be measured as an index of metabolism. Experiments are now in progress to adapt the procedures described by other investigators for the prepartion of rat hepatocytes to the preparation of mouse hepatocytes.